Ceftobiprole (Zevtera/Mabelio) is a fifth-generation cephalosporin for the treatment of hospital-acquired pneumonia: excluding ventilator-associated pneumonia and community-acquired pneumonia.
Ceftobiprole exerts its antibacterial activity by binding to important penicillin-binding proteins and inhibiting their transpeptidase activity which is essential for the synthesis of bacterial cell walls.
It has high affinity for penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus strains.
It retains its activity against strains that express divergent mecA gene homologues.
Ceftobiprole also binds to penicillin-binding protein 2b in Streptococcus pneumoniae, to penicillin-binding protein 2x in Streptococcus pneumoniae and to penicillin-binding protein 5 in Enterococcus faecalis.
Routes of administration-Intravenous.
Has shown in vitro antimicrobial activity against a broad range of Gram-positive and Gram-negative pathogens.
Among the Gram-positive pathogens, ceftobiprole has demonstrated good in vitro activity against methicillin-resistant Staphylococcus aureus, methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, as well as against strains of methicillin-resistant Staphylococcus aureus with reduced susceptibility to linezolid, daptomycin or vancomycin.
Ceftobiprole has activity against Streptococcus pneumoniae and Enterococcus faecalis, but not against Enterococcus faecium.
For Gram-negative pathogens, ceftobiprole has shown good in vitro activity against Haemophilus influenzae,
Pseudomonas aeruginosa and strains of Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis that do not produce extended-spectrum β-lactamases.
Ceftobiprole is inactive against strains that produce extended-spectrum β-lactamases.
Ceftobiprole has shown efficacy two large randomized, double-blind, phase 3 clinical trials for hospital-acquired and community-acquired pneumonia.
Ceftobiprole was non-inferior to ceftazidime plus linezolid in the treatment of hospital-acquired pneumonia (excluding ventilator-acquired pneumonia) and non-inferior to ceftriaxone with or without linezolid in the treatment of community-acquired pneumonia.
Ceftobiprole medocaril is the active moiety of the prodrug ceftobiprole medocaril and is available for intravenous treatment only.
The recommended dose is 500 mg as 2-hour infusion every 8 hours.
It is mainly excreted renally.
Dose adjustment is required for patients with moderate or severe renal impairment.
No adjustment is needed by gender, ethnicity or age, in severely obese patients or in patients with hepatic impairment.
It was found to be non-inferior to daptomycin with respect to overall treatment success in patients with complicated staff aureus bacteremia.